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- W2162273704 abstract "Although viable mice can be generated from induced pluripotent stem cells (iPSCs), the impact of accumulated mutations on the developmental potential of the resulting iPSCs remains to be determined. Here, we demonstrate that all-iPSC mice generated through tetraploid blastocysts complementation can tolerate the accumulation of somatic mutations for up to six generations using a Tet-on inducible reprogramming system. But, the viability of the all-iPS mice decreased with increasing generations. A whole-genome sequencing survey revealed that thousands of single-nucleotide variations (SNVs), including 44 non-synonymous ones, accumulated throughout the sequential reprogramming process. Subsequent analysis provides evidence that these accumulated SNVs account for the gradual reduction in viability of the resultant all-iPSC mice. Unexpectedly, our present reprogramming system revealed that pluripotent stem cells are heterogeneous in terms of possessing a set of copy-number alterations (CNAs). These CNAs are unique for pluripotent cells and subsequently disappear in the differentiating progenies. Mice can be generated from induced pluripotent stem cells (iPSCs) but the impact of accumulated mutations on the developmental potential of the cells remains to be determined. Here the authors show that mice generated from iPSCs tolerate the accumulation of somatic mutations for up to six generations, but their viability decreased with increasing generations." @default.
- W2162273704 created "2016-06-24" @default.
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- W2162273704 date "2015-02-18" @default.
- W2162273704 modified "2023-10-16" @default.
- W2162273704 title "Unique features of mutations revealed by sequentially reprogrammed induced pluripotent stem cells" @default.
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- W2162273704 doi "https://doi.org/10.1038/ncomms7318" @default.
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